scholarly journals 2841. A Phase 3, Randomized, Double-Blind Study Comparing Tedizolid Phosphate (TZD) and Linezolid (LZD) for Treatment of Ventilated Gram-Positive (G+) Nosocomial Pneumonia

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S67-S67
Author(s):  
Richard G Wunderink ◽  
Antoine Roquilly ◽  
Martin Croce ◽  
Daniel Rodriguez Gonzalez ◽  
Satoshi Fujimi ◽  
...  
Keyword(s):  
Clinical Response ◽  
Clinical Laboratory ◽  
Clinical Success ◽  
Incidence Rates ◽  
Double Blind Study ◽  
Phase 3 ◽  
Double Blind ◽  
Intent To Treat ◽  
Hospital Acquired

Abstract Background Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are frequently caused by G+ cocci; TZD has potent in vitro activity against these pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). The VITAL study compared the efficacy and safety of TZD vs. LZD for the treatment of ventilated patients with G+ HAP/VAP. Methods Randomized, double-blind, double-dummy, global, phase 3 study in mechanically ventilated adult patients with presumed G+ HAP/VAP (clinicaltrials.gov NCT02019420). Patients were stratified by region, age, and trauma/nontrauma, then randomized 1:1 to intravenous (IV) TZD 200 mg once daily for 7 days or IV LZD 600 mg every 12 h for 10 d (patients with concurrent G+ bacteremia received 14 d of treatment). The primary efficacy endpoint was day 28 all-cause mortality (ACM) in the intent to treat (ITT) population (all randomized patients; noninferiority [NI] margin, 10%). Secondary endpoints included investigator-assessed clinical response at test of cure (TOC; NI margin, 12.5%). Results In total, 726 patients were randomized (TZD n = 366; LZD n = 360). Baseline characteristics were well balanced between arms. TZD was noninferior to LZD for day 28 ACM in the ITT (table). Noninferiority was not demonstrated for TZD vs. LZD for investigator-assessed clinical success at TOC in the ITT. Stratification factors, analysis population, baseline clinical/laboratory signs of HAP/VAP, G+ only vs. mixed G+/gram-negative (G–) HAP/VAP, adjunctive G– therapy, MRSA vs. methicillin-susceptible S. aureus, and HAP vs. VAP were evaluated, and no single factor accounted for the observed imbalance in clinical response between treatment arms. Greater than 90% of patients experienced treatment-emergent adverse events (TEAEs). Anemia, hypokalemia, and diarrhea were the most frequently reported (TEAEs) in both arms. Types and incidence rates of TEAEs overall, and of drug-related TEAEs specifically, were comparable between TZD and LZD. Conclusion TZD was noninferior to LZD for day 28 ACM in the treatment of ventilated G+ HAP/VAP. However, TZD was not noninferior to LZD based on the investigator-assessed clinical response at TOC. Both drugs were similarly well tolerated and TEAEs were well balanced between groups, with no new safety signals identified. Disclosures All Authors: No reported Disclosures.

scholarly journals A Phase 3, Randomized, Double-Blind Study Comparing Tedizolid Phosphate and Linezolid for Treatment of Ventilated Gram-Positive Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia

2021 ◽  
Author(s):  
Richard G Wunderink ◽  
Antoine Roquilly ◽  
Martin Croce ◽  
Daniel Rodriguez Gonzalez ◽  
Satoshi Fujimi ◽  
...  
Keyword(s):  
Clinical Response ◽  
Bacterial Pneumonia ◽  
Double Blind Study ◽  
Phase 3 ◽  
Gram Positive ◽  
Double Blind ◽  
Intention To Treat ◽  
The Difference ◽  
Hospital Acquired ◽  
Noninferiority Margin

Abstract Background Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) are associated with high mortality rates. We evaluated the efficacy and safety of tedizolid (administered as tedizolid phosphate) for treatment of gram-positive ventilated HABP/VABP. Methods In this randomized, noninferiority, double-blind, double-dummy, global phase 3 trial, patients were randomized 1:1 to receive intravenous tedizolid phosphate 200 mg once daily for 7 days or intravenous linezolid 600 mg every 12 hours for 10 days. Treatment was 14 days in patients with concurrent gram-positive bacteremia. The primary efficacy end points were day 28 all-cause mortality (ACM; noninferiority margin, 10%) and investigator-assessed clinical response at test of cure (TOC; noninferiority margin, 12.5%) in the intention-to-treat population. Results Overall, 726 patients were randomized (tedizolid, n = 366; linezolid, n = 360). Baseline characteristics, including incidence of methicillin-resistant Staphylococcus aureus (31.3% overall), were well balanced. Tedizolid was noninferior to linezolid for day 28 ACM rate: 28.1% and 26.4%, respectively (difference, –1.8%; 95% confidence interval [CI]: –8.2 to 4.7). Noninferiority of tedizolid was not demonstrated for investigator-assessed clinical cure at TOC (tedizolid, 56.3% vs linezolid, 63.9%; difference, –7.6%; 97.5% CI: –15.7 to 0.5). In post hoc analyses, no single factor accounted for the difference in clinical response between treatment groups. Drug-related adverse events occurred in 8.1% and 11.9% of patients who received tedizolid and linezolid, respectively. Conclusions Tedizolid was noninferior to linezolid for day 28 ACM in the treatment of gram-positive ventilated HABP/VABP. Noninferiority of tedizolid for investigator-assessed clinical response at TOC was not demonstrated. Both drugs were well tolerated. Clinical Trials Registration NCT02019420.

scholarly journals 1230. Clinical and Microbiologic Outcomes by Causative Pathogen in Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia (HABP/VABP) Treated with Imipenem/Cilastatin (IMI)/Relebactam (REL) Versus Piperacillin/Tazobactam (PIP/TAZ)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S635-S635
Author(s):  
Maria C Losada ◽  
Alok Maniar ◽  
Jiejun Du ◽  
Michelle L Brown ◽  
Katherine Young ◽  
...  
Keyword(s):  
Clinical Response ◽  
Study Drug ◽  
Empiric Therapy ◽  
Causative Pathogen ◽  
Phase 3 ◽  
Double Blind ◽  
Mitt Population ◽  
Secondary Endpoints ◽  
Intent To Treat ◽  
Hospital Acquired

Abstract Background IMI/REL is a combination of IMI and the novel class A and class C β-lactamase inhibitor REL. Here we present per-pathogen outcomes from a recent phase 3 clinical trial (RESTORE-IMI 2), in which IMI/REL was shown to be non-inferior to piperacillin/tazobactam (PIP/TAZ) for empiric therapy of HABP/VABP, in both primary and key secondary endpoints. Methods Randomized, controlled, double-blind, multinational, phase 3, non-inferiority trial in adults with HABP/VABP. Lower respiratory tract specimens were obtained ≤48 hours prior to screening. Participants (pts) were randomized 1:1 to IMI/REL 500 mg/250 mg or PIP/TAZ 4 g/500 mg, given intravenously every 6 h for 7-14 d. Pts also received empiric linezolid until baseline cultures confirmed absence of MRSA. This analysis evaluated outcomes by causative LRT pathogen in modified intent to treat (MITT) pts (randomized pts with ≥1 dose of study drug, excluding pts with only gram-positive cocci present on baseline Gram stain) who had ≥1 baseline LRT pathogen susceptible (according to CLSI criteria) to both study drugs. Outcomes assessed were microbiologic response at end of therapy (EOT), clinical response at early follow-up (EFU; 7-14 d after EOT), and Day 28 all-cause mortality (ACM). Results Of 531 MITT pts, 51.4% (130 IMI/REL, 143 PIP/TAZ) had ≥1 baseline LRT pathogen susceptible to both study drugs. The most common causative pathogens in this analysis population were Klebsiella spp (30.4% of patients), Pseudomonas aeruginosa (22.3%), Escherichia coli (22.0%), and Haemophilus influenzae (9.2%), consistent with other recent trials in HABP/VABP and with surveillance data. Outcomes by pathogen were generally comparable between IMI/REL and PIP/TAZ (Table). In a separate subgroup analysis of the microbiologic MITT population, in pts with ≥1 ESBL-positive LRT pathogen (45 IMI/REL, 35 PIP/TAZ), microbiologic response at EOT was 82.2% (IMI/REL) vs 68.6%% (PIP/TAZ), clinical response at EFU was 64.4% vs 60.0%, and Day 28 ACM was 20.0% and 22.9%, respectively. In the IMI/REL arm, 8 pts had ≥1 confirmed KPC-positive baseline LRT pathogen; KPC status was not assessed in the PIP/TAZ arm. Conclusion IMI/REL is an efficacious treatment option for HABP/VABP, regardless of causative pathogen. Table. Primary and secondary efficacy outcomes in patients who were in the MITT population and had at least 1 baseline LRT pathogen susceptible to both study drugs Disclosures Maria C. Losada, BA, Merck & Co., Inc. (Employee, Shareholder) Jiejun Du, PhD, Merck & Co., Inc. (Employee, Shareholder) Michelle L. Brown, BS, Merck & Co., Inc. (Employee, Shareholder) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Robert Tipping, MS, Merck & Co., Inc. (Employee, Shareholder) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Joan R. Butterton, MD, Merck & Co., Inc. (Employee, Shareholder) Amanda Paschke, MD MSCE, Merck & Co., Inc. (Employee, Shareholder) Luke F. Chen, MBBS MPH MBA FRACP FSHEA FIDSA, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder)

scholarly journals RESTORE-IMI 1: A Multicenter, Randomized, Double-blind Trial Comparing Efficacy and Safety of Imipenem/Relebactam vs Colistin Plus Imipenem in Patients With Imipenem-nonsusceptible Bacterial Infections

2019 ◽  
Vol 70 (9) ◽  
pp. 1799-1808 ◽  
Author(s):  
Johann Motsch ◽  
Cláudia Murta de Oliveira ◽  
Viktor Stus ◽  
Iftihar Köksal ◽  
Olexiy Lyulko ◽  
...  
Keyword(s):  
Clinical Response ◽  
Bacterial Infections ◽  
Infection Type ◽  
Complicated Urinary Tract Infection ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Overall Response ◽  
Dose Study ◽  
Intent To Treat ◽  
Hospital Acquired

Abstract Background The β-lactamase inhibitor relebactam can restore imipenem activity against imipenem-nonsusceptible gram-negative pathogens. We evaluated imipenem/relebactam for treating imipenem-nonsusceptible infections. Methods Randomized, controlled, double-blind, phase 3 trial. Hospitalized patients with hospital-acquired/ventilator-associated pneumonia, complicated intraabdominal infection, or complicated urinary tract infection caused by imipenem-nonsusceptible (but colistin- and imipenem/relebactam-susceptible) pathogens were randomized 2:1 to 5–21 days imipenem/relebactam or colistin+imipenem. Primary endpoint: favorable overall response (defined by relevant endpoints for each infection type) in the modified microbiologic intent-to-treat (mMITT) population (qualifying baseline pathogen and ≥1 dose study treatment). Secondary endpoints: clinical response, all-cause mortality, and treatment-emergent nephrotoxicity. Safety analyses included patients with ≥1 dose study treatment. Results Thirty-one patients received imipenem/relebactam and 16 colistin+imipenem. Among mITT patients (n = 21 imipenem/relebactam, n = 10 colistin+imipenem), 29% had Acute Physiology and Chronic Health Evaluation II scores >15, 23% had creatinine clearance <60 mL/min, and 35% were aged ≥65 years. Qualifying baseline pathogens: Pseudomonas aeruginosa (77%), Klebsiella spp. (16%), other Enterobacteriaceae (6%). Favorable overall response was observed in 71% imipenem/relebactam and 70% colistin+imipenem patients (90% confidence interval [CI] for difference, –27.5, 21.4), day 28 favorable clinical response in 71% and 40% (90% CI, 1.3, 51.5), and 28-day mortality in 10% and 30% (90% CI, –46.4, 6.7), respectively. Serious adverse events (AEs) occurred in 10% of imipenem/relebactam and 31% of colistin+imipenem patients, drug-related AEs in 16% and 31% (no drug-related deaths), and treatment-emergent nephrotoxicity in 10% and 56% (P = .002), respectively. Conclusions Imipenem/relebactam is an efficacious and well-tolerated treatment option for carbapenem-nonsusceptible infections. Clinical Trials Registration NCT02452047.

scholarly journals Phase 2, Randomized, Double-Blind Study of the Efficacy and Safety of Two Dose Regimens of Eravacycline versus Ertapenem for Adult Community-Acquired Complicated Intra-Abdominal Infections

2013 ◽  
Vol 58 (4) ◽  
pp. 1847-1854 ◽  
Author(s):  
Joseph S. Solomkin ◽  
Mayakonda Krishnamurthy Ramesh ◽  
Gintaras Cesnauskas ◽  
Nikolajs Novikovs ◽  
Penka Stefanova ◽  
...  
Keyword(s):  
Clinical Success ◽  
Clinical Success Rate ◽  
Blind Study ◽  
Double Blind Study ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Gram Negative ◽  
Abdominal Infections

ABSTRACTEravacycline is a novel fluorocycline, highly active against Gram-positive and Gram-negative pathogensin vitro, including those with tetracycline and multidrug resistance. This phase 2, randomized, double-blind study was conducted to evaluate the efficacy and safety of two dose regimens of eravacycline compared with ertapenem in adult hospitalized patients with complicated intra-abdominal infections (cIAIs). Patients with confirmed cIAI requiring surgical or percutaneous intervention and antibacterial therapy were randomized (2:2:1) to receive eravacycline at 1.5 mg/kg of body weight every 24 h (q24h), eravacycline at 1.0 mg/kg every 12 h (q12h), or ertapenem at 1 g (q24h) for a minimum of 4 days and a maximum of 14 days. The primary efficacy endpoint was the clinical response in microbiologically evaluable (ME) patients at the test-of-cure (TOC) visit 10 to 14 days after the last dose of study drug therapy. Overall, 53 patients received eravacycline at 1.5 mg/kg q24h, 56 received eravacycline at 1.0 mg/kg q12h, and 30 received ertapenem. For the ME population, the clinical success rate at the TOC visit was 92.9% (39/42) in the group receiving eravacycline at 1.5 mg/kg q24h, 100% (41/41) in the group receiving eravacycline at 1.0 mg/kg q12h, and 92.3% (24/26) in the ertapenem group. The incidences of treatment-emergent adverse events were 35.8%, 28.6%, and 26.7%, respectively. Incidence rates of nausea and vomiting were low in both eravacycline groups. Both dose regimens of eravacycline were as efficacious as the comparator, ertapenem, in patients with cIAI and were well tolerated. These results support the continued development of eravacycline for the treatment of serious infections, including those caused by drug-resistant Gram-negative pathogens. (This study has been registered at ClinicalTrials.gov under registration no. NCT01265784.)

scholarly journals Ceftobiprole Compared With Vancomycin Plus Aztreonam in the Treatment of Acute Bacterial Skin and Skin Structure Infections: Results of a Phase 3, Randomized, Double-blind Trial (TARGET)

2020 ◽  
Author(s):  
J Scott Overcash ◽  
Charles Kim ◽  
Richard Keech ◽  
Illia Gumenchuk ◽  
Borislav Ninov ◽  
...  
Keyword(s):  
Clinical Response ◽  
Clinical Success ◽  
Laboratory Data ◽  
European Medicines Agency ◽  
Success Rates ◽  
Phase 3 ◽  
Gram Positive ◽  
Double Blind ◽  
Gram Negative ◽  
Skin Structure

Abstract Background The development of novel broad-spectrum antibiotics, with efficacy against both gram-positive and gram-negative bacteria, has the potential to enhance treatment options for acute bacterial skin and skin structure infections (ABSSSIs). Ceftobiprole is an advanced-generation intravenous cephalosporin with broad in vitro activity against gram-positive (including methicillin-resistant Staphylococcus aureus) and gram-negative pathogens. Methods TARGET was a randomized, double-blind, active-controlled, parallel-group, multicenter, phase 3 noninferiority study that compared ceftobiprole with vancomycin plus aztreonam. The Food and Drug Administration-defined primary efficacy endpoint was early clinical response 48–72 hours after treatment initiation in the intent-to-treat (ITT) population and the European Medicines Agency-defined primary endpoint was investigator-assessed clinical success at the test-of-cure (TOC) visit. Noninferiority was defined as the lower limit of the 95% CI for the difference in success rates (ceftobiprole minus vancomycin/aztreonam) >−10%. Safety was assessed through adverse event and laboratory data collection. Results In total, 679 patients were randomized to ceftobiprole (n = 335) or vancomycin/aztreonam (n = 344). Early clinical success rates were 91.3% and 88.1% in the ceftobiprole and vancomycin/aztreonam groups, respectively, and noninferiority was demonstrated (adjusted difference: 3.3%; 95% CI: −1.2, 7.8). Investigator-assessed clinical success at the TOC visit was similar between the 2 groups, and noninferiority was demonstrated for both the ITT (90.1% vs 89.0%) and clinically evaluable (97.9% vs 95.2%) populations. Both treatment groups displayed similar microbiological success and safety profiles. Conclusions TARGET demonstrated that ceftobiprole is noninferior to vancomycin/aztreonam in the treatment of ABSSSIs, in terms of early clinical response and investigator-assessed clinical success at the TOC visit. Clinical Trials Registration NCT03137173.

scholarly journals 2227. Outcomes in Patients with Renal Impairment from a Phase 3 Clinical Trial for Ceftolozane–Tazobactam (C/T) Treatment of Nosocomial Pneumonia (ASPECT-NP)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S760-S761
Author(s):  
Jennifer A Huntington ◽  
Brian Yu ◽  
Linping Li ◽  
Erin Jensen ◽  
Christopher Bruno ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Impairment ◽  
Nosocomial Pneumonia ◽  
Clinical Cure ◽  
Study Drug ◽  
Double Blind Study ◽  
Phase 3 ◽  
Double Blind ◽  
Intent To Treat ◽  
Cure Rates

Abstract Background ASPECT-NP, a phase 3, randomized, double-blind study, evaluated C/T (at double the approved dose for other indications) vs. meropenem (MEM) in adults with ventilated nosocomial pneumonia. We compared safety and efficacy outcomes from this trial among patients with and without renal impairment (RI). Methods Patients were stratified by age and diagnosis and were randomized 1:1 to intravenous (IV) C/T 3 g every 8 h or IV MEM 1 g every 8 h. Study drug was administered for 8–14 days; doses were adjusted for moderate and severe RI. Eligible patients were mechanically ventilated; those on renal replacement therapy or with creatinine clearance (CrCL) < 15 mL/minute were excluded. Key efficacy endpoints included clinical cure rates at the test of cure (TOC) visit in the intent-to-treat (ITT) and clinically evaluable (CE) populations and Day 28 all-cause mortality (ACM) in the ITT population. In this analysis, patients were stratified based on renal function for outcome comparisons: normal renal function (CrCL ≥ 80 mL/minute); mild RI (CrCL > 50 to < 80 mL/minute); moderate RI (CrCL ≥ 30 to ≤ 50 mL/minute); and severe RI (CrCL ≥ 15 to < 30 mL/minute). Results A total of 726 patients were enrolled (C/T, N = 362; MEM, N = 364). Clinical cure rates at the TOC visit (CE and ITT populations) were robust across CrCL subgroups in both treatment arms and were similar based on 95% confidence intervals for treatment differences that included 0 (table). Day 28 ACM rates for patients with moderate and severe RI were numerically higher than those with mild RI in the MEM treatment arm. Rates of treatment-emergent adverse events (TEAEs) were similar in both treatment arms and across CrCL subgroups, with rates generally increasing with increasing RI severity. Rates of treatment-related TEAEs were low across treatment arms and CrCL subgroups with no treatment-related deaths reported. Conclusion Similar clinical cure and Day 28 ACM rates at the TOC visit were found across treatment groups for all CrCL subgroups, consistent with the overall primary and key secondary efficacy results for the ASPECT-NP study. Both drugs were well-tolerated. The results of this analysis indicate that the use of dose-adjusted C/T is appropriate in patients with nosocomial pneumonia and moderate or severe RI. Disclosures All authors: No reported disclosures.

scholarly journals 2228. Treatment of Community-Acquired Bacterial Pneumonia (CABP) in Patients with Diabetes: Outcomes from a Global Phase 3 Study of Delafloxacin (DLX)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S761-S761
Author(s):  
Igor Kaidashev ◽  
Mimi Nitu ◽  
Monica Popescu ◽  
Laura Lawrence ◽  
Megan Quintas ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Clinical Success ◽  
Signs And Symptoms ◽  
Patient Characteristics ◽  
Qt Prolongation ◽  
Phase 3 ◽  
Double Blind ◽  
Challenge Study ◽  
Patients With Diabetes ◽  
Intent To Treat

Abstract Background Delafloxacin (DLX) is an IV/oral anionic fluoroquinolone with no QT restrictions. It is approved for the treatment of serious skin infections including those due to MRSA and Gram-negative pathogens. A Phase 3 trial of patients with CABP was recently completed comparing DLX to moxifloxacin (MOX), including patients with diabetes (DM). Methods Multicenter, randomized, double-blind trial of adults with CABP with at least 2 clinical symptoms; physical signs; and radiographic evidence of pneumonia. Patients were randomized 1:1 to DLX or MOX treatment for 5–10 days. Patients received a minimum of 3 days of IV treatment, then were switched to oral at MD discretion. Key endpoints were the Early Clinical Response (ECR) at 96 ±24h and the investigator assessment of response at Test of Cure (TOC) 5–10 days after last dose in the Intent to Treat population. Clinical success was defined as complete or near resolution of signs and symptoms and no further antibiotics needed per investigator assessment. Results 131 DM patients were randomized. Patient characteristics: 59% male; mean age 66 (26% ≥ age 75); 40% PORT class IV/V; 29% multi-lobar pneumonia. Bacterial pathogens were identified in 59% at baseline. Patients received treatment ~8.5 days. DLX was comparable to MOX in patients with DM, with response at ECR 90% DLX vs. 88.5% MOX [1.5 (95% CI -9.6, 13.2)] as well as Clinical Success at TOC 87.1% DLX vs. 86.9% MOX [0.3 (95% CI −11.6, 12.7)]. The overall % of DM patients with at least one treatment-related adverse event (AE) was 18.6% DLX and 11.7% MOX. The most frequent treatment-related adverse events were gastrointestinal in nature including diarrhea seen in 6 DLX and 2 MOX patients.There were 3 DLX and 2 MOX deaths of patients with DM during the study (up to Day 28), unrelated to treatment. There were no cases of C diff in these patients. There were no reports of hypoglycemia on DLX. There was one discontinuation of treatment due to a related AE in each treatment group. Conclusion IV/oral DLX was comparable to IV/oral MOX for treatment of CABP in patients with diabetes. DLX has no preclinical signals for QT prolongation and has no QT prolongation in a validated challenge study. There were no events of hypoglycemia. DLX appears effective and well tolerated in patients with diabetes and CABP. Disclosures All authors: No reported disclosures.

scholarly journals A Phase-3 Study to Compare Delafloxacin to Moxifloxacin for the Treatment of Adults with Community-acquired Bacterial Pneumonia (DEFINE-CABP)

2019 ◽  
Author(s):  
Juan P Horcajada ◽  
Robert A Salata ◽  
Rodolfo Álvarez-Sala ◽  
Floarea Mimi Nitu ◽  
Laura Lawrence ◽  
...  
Keyword(s):  
Clinical Response ◽  
Bacterial Pneumonia ◽  
Study Drug ◽  
The United States ◽  
Efficacy And Safety ◽  
Success Rates ◽  
Phase 3 ◽  
Double Blind ◽  
Atypical Pathogens ◽  
Intent To Treat

Abstract Background The clinical and economic burden of community-acquired bacterial pneumonia (CABP) is significant and is anticipated to increase as the population ages and pathogens become more resistant. Delafloxacin is a fluoroquinolone antibiotic approved in the United States for the treatment of adults with acute bacterial skin and skin structure infections. Delafloxacin’s shape and charge profile uniquely impacts its spectrum of activity and side effect profile. This phase 3 study compared the efficacy and safety of delafloxacin to moxifloxacin for the treatment of CABP. Methods A randomized, double-blind, comparator-controlled, multicenter, global Phase 3 study compared the efficacy and safety of delafloxacin 300 mg BID or moxifloxacin 400 mg QD in adults with CABP. The primary endpoint was early clinical response (ECR) defined as improvement at 96 (± 24) hours after first dose of study drug. Clinical response at test of cure (TOC) and microbiologic response were also assessed. Results In the intent-to-treat analysis population (ITT), ECR rates were 88.9% in the delafloxacin group and 89.0% in the moxifloxacin group. Noninferiority of delafloxacin compared with moxifloxacin was demonstrated. At TOC in the ITT population, the success rates were similar between groups. Treatment-emergent adverse events considered at least possibly related to the study drug occurred in 65 subjects (15.2%) in the delafloxacin group and 54 (12.6%) in the moxifloxacin group. Conclusions IV/oral delafloxacin monotherapy is effective and well tolerated in the treatment of adults with CABP, providing coverage for grampositive, gramnegative, and atypical pathogens.

scholarly journals 2234. Outcomes by Age and Gender from a Global Phase 3 Study of Delafloxacin (DLX) in Community-Acquired Bacterial Pneumonia (CABP)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S763-S763
Author(s):  
Andrzej Madej ◽  
John Pullman ◽  
Monica Popescu ◽  
Megan Quintas ◽  
Laura Lawrence ◽  
...  
Keyword(s):  
Clinical Success ◽  
Signs And Symptoms ◽  
The United States ◽  
Qt Prolongation ◽  
Phase 3 ◽  
Double Blind ◽  
Age And Gender ◽  
Promising Alternative ◽  
And Gender ◽  
Intent To Treat

Abstract Background Delafloxacin (DLX) is a fluoroquinolone, approved in the United States for treatment of ABSSSI. DLX has no preclinical signals for QT prolongation and has no QT prolongation in a validated challenge study. Risk of QT prolongation is a consideration in antibiotic selection for elderly hospitalized CABP patients. A Phase 3 CABP trial with DLX was analyzed with a focus on age and gender. Methods Data on age and gender were reviewed from a multicenter, randomized, double-blind trial of adults with CABP. Patients were randomized 1:1 to DLX or moxifloxacin (MOX) treatment for 5–10 days. Patients received a minimum of 3 days of IV treatment, then were switched to oral at MD discretion. A key clinical endpoint was the investigator-assessment at Test of Cure (TOC) 5–10 days after the end of treatment. Clinical success was defined as complete or near resolution of signs and symptoms and no further antibiotics needed Results In the overall study, 859 patients were randomized with a mean age of 60 years (55.5% <65, 44.5% ≥65, 21.2% ≥75; range 18–93); 58.7% were male; 25.4% and 1.4% were PORT class IV and V; 28.6% multi-lobar pneumonia. Table shows the comparison of DLX and MOX clinical response at TOC in the Intent to Treat (ITT) population. Overall, DLX was well tolerated, with similar related adverse events (AE) between treatment groups regardless of age (< 65: 16.7% DLX, 13.3% MOX; ≥ 65: 13.4% DLX, 11.7% MOX) or gender (male: 16.0% DLX, 11.1% MOX; female 14.0% DLX, 14.9% MOX). The most common treatment-related AEs for DLX were diarrhea and transaminase elevations which were mild-to-moderate and did not routinely lead to discontinuation. There were no reports of potential QT prolongation on DLX. Conclusion Based on age and gender, DLX had comparable outcomes to MOX in clinical success at TOC. DLX was also well tolerated regardless of age or gender. DLX may offer a promising alternative in the treatment of CABP including elderly patients. Disclosures All authors: No reported disclosures.

The Effect of Warfarin Sodium on the Duration of Platelet Aggregation

1967 ◽  
Vol 18 (03/04) ◽  
pp. 766-778 ◽  
Author(s):  
H. J Knieriem ◽  
A. B Chandler
Keyword(s):  
Platelet Count ◽  
Placebo Group ◽  
Platelet Aggregation ◽  
Prothrombin Time ◽  
Platelet Rich Plasma ◽  
Healthy Adults ◽  
Double Blind Study ◽  
Double Blind ◽  
Warfarin Sodium

SummaryThe effect of the administration of warfarin sodium (Coumadin®) on the duration of platelet aggregation in vitro was studied. Coumadin was given for 4 consecutive days to 10 healthy adults who were followed over a period of 9 days. The duration of adenosine diphosphate-induced platelet aggregation in platelet-rich plasma, the prothrombin time, and the platelet count of platelet-rich plasma were measured. Four other healthy adults received placebos and participated in a double-blind study with those receiving Coumadin.Although administration of Coumadin caused a prolongation of the prothrombin time to 2 or 21/2 times the normal value, a decrease in the duration of platelet aggregation was not observed. In most individuals who received Coumadin an increase in the duration of platelet aggregation occurred. The effect of Coumadin on platelet aggregation was not consistently related to the prothrombin time or to the platelet count. In the placebo group there was a distinct relation between the duration of platelet aggregation and the platelet count in platelet-rich plasma.The mean increase in the duration of platelet aggregation when compared to the control value before medication with Coumadin was 37.7%. In the placebo group there was a mean increase of 8.4%. The difference between the two groups is significant (p <0.001). Increased duration of platelet aggregation also occurred in two individuals who received Coumadin over a period of 10 and 16 days respectively.

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